Immunohisthochemical Analysis of P-Stage I Large Cell Neuroendocrine Carcinoma of the Lung: Analysis of Adhesion Molecules and Proliferative Activity - Abstract
A Large Cell Neuroendocrine Carcinoma (LCNEC) of the lung is highly malignant. Reduced or abnormal expression of adhesion molecules, such as E-cadherin and b-catenin, on the cell membrane is associated with the aggressiveness of its tumor cells, while nuclear b-catenin activates the WNT signaling pathway. To examine the mechanism of LCNEC aggressiveness, we used immunohistochemistry to examine the expressions of E-cadherin and b-catenin in the membrane, as well as the nuclear expression of b-catenin and Ki-67 labeling index in 12 pathological (p)-stage I LCNEC specimens. As a control, we used solid-sheet components from 19 p-stages I solid predominant Poorly Differentiated Adenocarcinomas (PDAs), as that tumor is the most aggressive among non-small cell carcinomas of various histological types. The diseasefree rate of patients with LCNEC was much lower than that of patients with PDA. In the LCNECs, there was no significant difference in the frequency of membrane-expression of E-cadherin and b-catenin, though all specimens predominantly showed disrupted patterns of membrane staining for both E-cadherin and b-catenin, while 16 of 19 PDAs predominantly showed a linear pattern. Nuclear b-catenin staining was found in 4 of 13 LCNECs, but in none of the PDAs. The Ki-67 labeling index of the LCNEC specimens was about 4-fold greater than that of the PDAs. The present results suggest that abnormal membrane expression of E-cadherin and b-catenin, nuclear b-catenin expression, and high proliferative potential are associated with LCNEC aggressiveness.